The mechanism of enzyme induction in response to 3',5'-cyclic nucleotides will be studied in established lines of rat hepatoma cells in culture. The major response to be investigated is the increased synthesis of tyrosine aminotransferase produced by derivatives of cyclic AMP. The proposed project will attempt to determine whether cyclic AMP alters transcription, translation, or some other step to induce tyrosine aminotransferase in the hepatoma cells. The role of cyclic AMP-dependent protein kinases in the induction mechanism will be explored. In addition, the possibility that cyclic nucleotides are involved in controlling the degradation of tyrosine aminotransferase will be investigated. Comparisons will be made with liver to elucidate possible differences between normal and malignant cells in cyclic nucleotide responses and in the components with which cyclic nucleotides interact. These studies should lead to a greater understanding of the function of cyclic nucleotides as mediators of hormone action and as metabolic regulators in normal and neoplastic cells.